System and method for bronchial dilation

ABSTRACT

A method of reducing bronchial constriction in a subject includes delivering energy to create one or more lesions on a main bronchus so as to transect pulmonary nerves sufficiently to reduce bronchial constriction in a lung of the patient distal to the main bronchus.

RELATED APPLICATIONS

This application is a continuation of application Ser. No. 15/853,030filed Dec. 22, 2017, which in turn is a continuation of application Ser.No. 15/401,825 filed Jan. 9, 2017, now U.S. Pat. No. 9,867,986 issuedJan. 16, 2018, which in turn is a continuation of application Ser. No.14/841,836 filed Sep. 1, 2015, now U.S. Pat. No. 9,539,048 issued Jan.10, 2017, which in turn is a continuation of application Ser. No.14/265,443 filed Apr. 30, 2014, now U.S. Pat. No. 9,125,643 issued Sep.8, 2015, which in turn is a continuation of application Ser. No.13/920,801 filed Jun. 18, 2013, now U.S. Pat. No. 8,731,672 issued May20, 2014, which in turn is a continuation of U.S. patent applicationSer. No. 13/523,223 filed Jun. 14, 2012, now U.S. Pat. No. 8,489,192issued Jul. 16, 2013, which in turn is a continuation of U.S. patentapplication Ser. No. 12/372,607 filed Feb. 17, 2009, now U.S. Pat. No.8,483,831 issued Jul. 9, 2013, which in turn claims the benefit of U.S.Provisional Application No. 61/066,026 filed Feb. 15, 2008, and U.S.Provisional Application No. 61/049,605 filed May 1, 2008, each of whichis hereby fully incorporated herein.

TECHNICAL FIELD

This document pertains generally to medical devices, and moreparticularly, but not by way of limitation, to systems and methods forbronchial stimulation.

BACKGROUND

Obstructive pulmonary disease, including asthma, emphysema, or chronicbronchitis, afflicts more than 25 million individuals in the UnitedStates and accounted for over 17 million physician office visits in themid 1990's. Current estimates for the total cost of these diseases arein excess of $20 billion. These diseases are increasing in prevalencedue to myriad causal factors, but principally driven by smoking.

While a chronic disease, the hallmark of asthma is acute episodes ofdifficulty breathing created by an acute constriction of smooth muscleslining the bronchi (the passage ways for air in the lungs), reducing thediameter of the airway and increasing the resistance to air flow.Bronchial constriction in asthma is “reversible” in that the acuteconstriction can be reversed by bronchodilation medication or by thepassage of time (after removal of the irritant that elicited theconstriction). However, asthma chronically exhibits itself asinflammation, hypertrophy, or hyper-excitability of the smooth muscles.

Emphysema and chronic bronchitis are different diseases than asthma, butcan be related by the same causal factor and concomitant appearance inthe same or similar individuals. Both emphysema and chronic bronchitisare predominantly caused by smoking and usually both exist in the sameindividual, hence they can be lumped together under the umbrella termChronic Obstructive Pulmonary Disease (COPD). However, the diseases arevery different and manifest themselves quite differently. While mostsubjects exhibit some amount of both diseases, a subject can becategorized by which condition is predominant in the subject's anatomy.

In emphysema, long term exposure to smoke or other noxious substancescan result in a primary breakdown of the lung parenchyma (alveoli,etc.). Normal fine alveoli can break down and form large open “holes”(bullea), which in turn can result in reduced surface area for gasexchange, sapping of inhaled air flow from healthy lung tissue, orreduced anchoring of bronchi that can result in airway collapse.

In chronic bronchitis, irritation of the bronchi can result ininflammation, hypertrophy, or constriction of the smooth muscles liningthe bronchi, or excessive mucus production that can clog the bronchi.While the smooth muscle contraction in chronic bronchitis is not as“reversible” as that exhibited in asthma, there is usually a significantdegree of reversibility and bronchodilator medications can be used as afirst line of therapy.

OVERVIEW

Chronic bronchitis and asthma can both exhibit airway smooth muscleconstriction resulting in airway constriction. The present inventorshave recognized, among other things, that bronchodilation medicationscan be used as a front lines therapy, but are far from optimaltreatments, as the efficacy of bronchodilation medications can belimited and subject compliance is often poor between episodes ofexacerbation. Further, the present inventors have recognized thatinhalers are difficult to use properly and are especially difficult forthe elderly (e.g., COPD) and children (e.g., asthma) to use optimally.Thus, the present inventors have recognized that a system or methodconfigured to chronically dilate the bronchi such as by decreasing,inhibiting, or eliminating smooth muscle contraction would be beneficialfor many subjects.

An implantable signal generator can be configured to generate a blockingsignal to be delivered to at least a portion of a bronchus. The blockingsignal can be configured to inhibit nerve traffic both to and from thelungs, to relieve bronchial smooth muscle contraction, and to inhibitcough. The implantable signal generator can be communicatively coupledto a processor configured to control delivery of the blocking signal,using received information about an indication of cough, to inhibitcough.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, which are not necessarily drawn to scale, like numeralsmay describe similar components in different views. Like numerals havingdifferent letter suffixes may represent different instances of similarcomponents. The drawings illustrate generally, by way of example, butnot by way of limitation, various embodiments discussed in the presentdocument.

FIG. 1 illustrates generally an example of a system including animplantable signal generator and a processor.

FIG. 2 illustrates generally an example of a system including a coughsensor, a user-interface, and a mucus sensor.

FIG. 3 illustrates generally an example of a method includingcontrolling delivery of a blocking signal to inhibit cough.

FIG. 4 illustrates generally an example of a method includingcontrolling delivery of a blocking signal to inhibit cough, or to allowmucus clearance.

FIG. 5 illustrates generally an example of a method including deliveringa blocking signal.

FIGS. 6A-6B illustrate generally structures in a thorax during access.

FIGS. 7-10 illustrate generally examples of various signal generatorimplant sites, lead paths, electrode sites, and electrodeconfigurations.

FIGS. 11A-11C illustrate generally example electrode configurations in,on, or surrounding at least a portion of a bronchus.

FIGS. 12A-12D illustrate generally an endo-bronchial electrodeconfiguration and approach.

FIG. 13 illustrates generally a relationship between a bony structureand lungs, and an example of accessing the root of the main bronchiusing two ports.

DETAILED DESCRIPTION

The present inventors have recognized, among other things, a system andmethod for chronically dilating the bronchi, such as by decreasing,inhibiting, or eliminating smooth muscle contraction.

General Anatomy

In general, the peripheral nervous system can be divided into thesomatic nervous system, the enteric nervous system, and the autonomicnervous system. The autonomic nervous system includes autonomic sensoryneurons, integrating centers in the central nervous system (e.g., thebrain), and autonomic motor neurons. A continual flow of nerve impulsesfrom autonomic sensory neurons in visceral organs (e.g., afferentnerves) and blood vessels propagate into integrating centers in thecentral nervous system. Further, impulses in autonomic motor neurons(e.g., efferent nerves) can propagate to various effector tissues. Thisinteraction between afferent and efferent propagation regulates theactivity of smooth muscles and glands throughout the body.

Autonomic motor neurons have two principal branches: the sympatheticdivision and the parasympathetic division. Many organs have dualinnervation from each of the branches. In general, nerve impulses fromone division stimulates the organ to increase its activity (excitation),and impulses from the other division decrease the organ's activity(inhibition).

The balance between sympathetic and parasympathetic activity is termed“autonomic tone” and establishes the status of the organ. The balance isregulated by the hypothalamus, which typically turns up sympathetic tonewhile simultaneously turning down parasympathetic tone, and vice-versa.

High sympathetic tone supports body functions that support vigorousactivity such as increased heart rate, increased blood pressure, etc.High parasympathetic tone supports “rest and digest” functions and hasthe opposite effect of sympathetic tone. Classically, human airwaydilation was considered to be driven by the activation of thesympathetic division. However, other theories suggest that human airwaysmooth muscle is largely devoid of sympathetic innervation, and thatdilation is derived from a different type of parasympathetic nerve.

Most parasympathetic nerves are termed “cholinergic” due to their use ofthe chemical acetylcholine during firing. Most sympathetic nerves aretermed “adrenergic” due to their use of adrenal gland substances duringfiring. However, additional species such as non-cholinergic,non-adrenergic parasympathetic nerves exist.

The distribution and function of parasympathetic-cholinergic nerves isconsistent across species. By contrast, the distribution and function ofsympathetic and non-cholinergic parasympathetic innervation of airwaysmooth muscle varies considerably between species. Human airway smoothmuscle is largely devoid of sympathetic adrenergic innervation.Non-adrenergic, non-cholinergic neurotransmitters (likely derived fromthe parasympathetic nerves) mediate the relaxations induced by the onlydemonstrably functional relaxant innervation of human airway smoothmuscle.

In cats, guinea pigs, and ferrets, non-cholinergic parasympathetictransmitters are not co-released with acetylcholine from a singlepopulation of postganglionic parasympathetic nerves. Rather, ananatomically and functionally distinct parasympathetic pathway regulatesnon-adrenergic, non-cholinergic relaxations of airway smooth muscle.Reflexes differentially regulate the cholinergic and non-cholinergicnerves. Further, the parasympathetic innervation of human airways can besimilar to that of cats and guinea pigs.

Both afferent and efferent parasympathetic nerves to the lungs derivefrom the vagus nerves at or near the pulmonary plexuses. The vagusnerves generally run roughly parallel to or lateral to the esophagus andtrachea, while the plexuses are in turn further lateral than the vagi.The plexuses lie on or near the main bronchi near their bifurcation, andthe nerves follow the branching of the bronchial tree within the lungparenchyma. Anantomists recognize both anterior and posterior plexuses(or equivalently the ventral and dorsal aspects). However, theanterior/ventral pulmonary plexus can be quite minor compared to theposterior/dorsal plexus. Further, the sympathetic innervation of thelungs pass through the pulmonary plexuses.

Basic Cholinergic Tone

Generally, airway parasympathetic nerves are tonically active duringtidal breathing and typically produce a stable, readily reversiblebaseline obstruction of the airways reflecting opposing influences ofcontractile and relaxant airway parasympathetic nerves acting on airwaysmooth muscle.

Constriction of the smooth muscle by activation of efferentparasympathetic nerves can obliterate the lumen of small bronchi andbronchioles, markedly increasing airway resistance in larger,cartilaginous airways. Conversely, bronchodilation can be induced bywithdrawing ongoing parasympathetic activity.

Sensory input from the lungs (e.g., via afferent nerves) can play asignificant role in the creation of basal tone. Further, deregulation ofbasal tone, such as that seen in bronchitis or asthma, can originatefrom altered afferent signaling. A recurring presence and level ofbaseline tone in the airways can imply the existence of a “set point”for smooth muscle contraction. In certain examples, a withdrawal oraugmentation of tone can be achieved in response to physiological orpathophysiological stimuli. Alterations in afferent or efferent nervefunction can contribute to airway hyperresponsiveness and airwayobstruction in diseases such as asthma or COPD.

In an example, cholinergic nerve activity in the airways can depend oninput from afferent (e.g., mechanically sensitive) nerve fibersinnervating the intrapulmonary airways and lungs. In certain examples,unilateral or bilateral severing of the afferent (sensory) nerves at thevagus can lead to a decrease in pulmonary resistance, indicating airwaydilation.

In certain examples, such as during extreme circumstances (e.g.,aspiration of foreign body, near drowning, trauma to the chest wall,etc.), a reflex bronchospasm may confer some physiologic benefit.Additionally, cholinergic tone may serve to minimize the work ofbreathing under the full variety of breathing states in a healthyindividual (e.g., rest, exercise, etc). Further, afferent nervesignaling can be important for the maintenance of other functions, suchas cough or mucus clearance. However, under non-extreme circumstances,the complete abolition of smooth muscle tone appears to have little orno physiological downside in a healthy individual. Moreover, in adiseased individual suffering from an obstructive disorder, the completeabolition of smooth muscle tone should be uniformly beneficial

Vagotomy

Generally, blocking the vagal nerves, such as by administering atropinesulfate to block postganglionic cholinergic pathways, by cooling of thenerve, or other blocking of the vagal nerves can result in dilation ofthe airways. Alternatively, surgical transaction of the vagus nerves canserve the same purpose. Historically, high vagal transection (in theneck region) has been used to treat asthma and COPD with some success.However, since the vagus nerve controls many body functions and organsother than the lungs, surgical transaction of the vagus carrysignificant complications and has not been adopted.

In a different example, lung transplant recipients can have denervatedlungs while their vagus nerves are intact. In these subjects, bronchialdiameters can be 150-200% of their normal pre-transplant bronchialdiameter. While surgical pulmonary denervation can be an effectivetherapy for asthma or chronic bronchitis, the effect is typically shortlived. The parasympathetic ganglia are typically located within theairways themselves. Generally, within the reimplanted lung,preganglionic fibers degenerate, but ganglia and undividedpostganglionic fibers do not. In these instances, because theregenerating preganglionic axons are located only a few centimeters fromthe line of division, reinnervation can occur rapidly. In certainexamples seen in animal models, pulmonary reinnervation can occur withina short period of time (e.g., three months), re-establishing autonomictone.

Notably, other potentially beneficial side effects can be seen insubjects having denervated lungs. For example, mucus production can bedecreased, and cough can be suppressed. In other examples, the sensationof dyspnea can be suppressed.

The present inventors have recognized, among other things, that achronic, minimally invasive, and reversible system and method can beprovided to increase the bronchial diameter of a subject. Further, thepresent inventors have recognized that while therapy can be directedtoward the vagus nerves, there are benefits to directing the therapymore distally, toward the pulmonary parasympathetic nerves, thuslimiting the effect to only the lungs and avoiding complications toother organs.

Mediastinoscopy

The mediastinum includes the region in mammals between the pleural sacscontaining the heart and all of the thoracic viscera except the lungs.The mediastinum can be accessed using a minimally invasive procedure,such as mediastinoscopy or videomediastinoscopy. These minimallyinvasive procedures can generally be used to biopsy many of the lymphnodes in this region to aid in the staging determination of variouscancers, and can generally be regarded as “day surgeries” having minimalmorbidity and fast recovery.

In an example, mediastinoscopy can allow access to the trachea and tothe main bronchi distal to the bifurcation. Access can be initiated atthe suprasternal notch where dissection can be carried out down to thetrachea. The plane of the pre-tracheal fascia can be used to carry thedissection down to the carina (bifurcation of the main bronchi). Inanother example, the Chamberlain procedure can allow access to the hilarareas of the lungs, e.g., using an initial incision at the 3rdintercostal space.

Mediastinoscopy can be performed by a thoracic surgeon with the subjectunder general anesthesia. While a host of large vascular structures runthrough this area, the procedure is generally safe and is the goldstandard for lymph node biopsies, commonly having reported morbidity andmortality rates of 0.6% and 0.2%, respectively.

The pulmonary nerves located on the anterior and posterior aspects ofthe bronchi are available for therapy using the minimally invasivemediastinoscopic approach to the main bronchi.

Video-Assisted Thoracic Surgery

Mediastinoscopy typically does not expose the distal portion of the mainbronchi or the dorsal aspect of the main bronchi. Thus, the presentinventors have recognized that it may be advantageous to use othersurgical techniques to access the bronchi.

In an example, video-assisted thoracic surgery (VATS) can be used toaccess structures on the thoracic wall (e.g., the sympathetic chainrunning parallel and lateral to the spinal column) or the lung itself(e.g., for a biopsy, wedge resection, etc.). In a VATS procedure, thelungs can be intubated with a bifurcated endotracheal tube, such thateach lung can be ventilated independently. Thus, one lung can beventilated while the other lung is deflated to provide working room inthat side of the chest cavity.

In certain examples, one or more ports (typically less than 5) can beplaced between ribs for access to the working space between the deflatedlung and the intact chest wall. An elongate scope or camera can beinserted, as well as auxiliary tools, in one or more ports. While portsare typically used for convenience (to maintain easy access to insertand withdraw tools), a physical port is not strictly necessary. A portcan include a physical port or a small incision between ribs without thephysical port.

In an example, during a procedure, a subject can be positioned lying onone side with the upper arm raised overhead, thereby allowing the one ormore ports to be placed in the ventral or dorsal portion of the chestwall and allowing the lung to be retracted either dorsally or ventrally.In an example, if a bilateral procedure is desired, the subject can berepositioned to the contralateral side during the procedure. In certainexamples, the subject can be positioned in a prone posture so both sidesof the chest cavity can be accessed without repositioning the subject.Further, the prone position allows the deflated lung to fall ventrally,naturally exposing the seam between the visceral and parietal pleura atthe posterior (e.g., dorsal) aspect of the main bronchi. In otherexamples, other endoscopic procedures can be used to implant at leastone of an electrode, a lead, or an implantable signal generator.

Therapy

In an example, surgical transection of the pulmonary nerves can abolishtonic smooth muscle tone. However, as discussed above, the duration ofthe effect can be limited. In certain examples, the duration can be asshort as 3 to 12 months before re-innervation can occur.

As a result, several other approaches can be considered. In an example,the pulmonary nerves can be transected at several locations using aseries of lesions (e.g., linear or other) created around at least aportion of the circumference of the bronchi. In an example,electrocautery can be used to create one or more linear lesions. Incertain examples, two or more lesions can be created, separated by gaps,such as 2 mm to 15 mm gaps.

In other examples, an implant having a bioactive component or coating(e.g., that suppresses neuron growth or regeneration) can be attached orotherwise placed on or around the bronchi to prevent the severed nervesfrom reinnervating. In certain examples, the coating can be similar toor the same as the coating used on drug coated stents placed in theheart (e.g., paclitaxel or serolimus), which are known to suppresscellular proliferation

In an example, an active implantable system, such as an implantablesignal generator and lead system, can be provided, portions of which canbe placed on or around the bronchi. Because afferent signals from thelungs are typically needed to produce the tonic smooth muscle tone, andbecause the tone is generally triggered by efferent parasympatheticfibers, substantially inhibiting or blocking nerve signals at thebronchi can serve the dual purpose of blocking both outgoing andincoming signals from the lungs. In this example, afferent signalinginto the integrating centers in the central nervous system and outgoingsignals to the smooth muscles can both be inhibited, effectivelycreating a “belt and suspenders” redundancy.

In an example, efferent and afferent parasympathetic and sympatheticnerve signals can be substantially inhibited or blocked at the bronchi.In certain examples, the inhibition or blocking can be accomplishedwithout providing efferent or afferent stimulation (e.g., inducingaction potentials) to the sympathetic or parasympathetic nerves at ornear the bronchi.

Blocking

In an example, nerve “blocking” can be realized by placing one or morenerve cuffs or other electrodes near the post-ganglionic ascendingafferent pulmonary nerves and post-ganglionic descending efferentpulmonary nerves on each pulmonary trunk. In other examples, the nerve“blocking” can be realized by placing one or more nerve cuffs on thepre-ganglionic vagus nerves on each pulmonary trunk, or by placing oneor more other electrodes (e.g., nerve stimulation patch electrodes, suchas an internal or external surface, plunge, or other electrodeconfiguration) on the pulmonary nerve plexus or ganglia. In certainexamples, other blocking electrodes can be placed elsewhere within orthroughout the upper bronchial tree or trachea, e.g., to further or morefinely control the blocking. In an example, one or more leads connectingone or more electrodes to a signal generator can exit the mediastinumthrough the surgeon's access route and can be tunneled subcutaneouslyfrom the suprasternal skin incision to a convenient location for theimplanted signal generator.

In an example, the blocking signal can be on the order of 10-5000 Hertz(in some cases higher than 5000 Hertz), 0.1-10 mA, with a pulse width of50 μs-2 ms. In other examples, other blocking signals having differentranges can be used, or a clamping signal, such as a voltage or currentclamping signal, can be applied. In certain examples, the clampingsignal can bias a cell such that an action potential can be prohibited.

Duty Cycle

In certain examples, the implantable system can be controlled using aduty cycle. In an example, because the signal generator is implantable,conservation of battery power can be important. Various duty cyclingschemes can be applied to conserve power. In certain examples, theimplantable system can include the ability to program electrostimulationduty cycle (e.g., on a percentage basis, such as from 1% to 100%; suchas “on” for 5% of the stimulation period (1/frequency), on a recurringcycle duration basis, such as “on” for x of y seconds, such as “on” for1 second out of 100 seconds up to “on” for 100 seconds out of 100seconds, or other time measures, such as minutes, hours, or days).

Physiologic Adaption Avoidance and/or Functional Allowance

In an example, the implantable system can be programmed to pause therapydelivery for a variable amount of time and then have therapy resume, orto modify/modulate one aspect of therapy delivery, such as changing thestimulation frequency or duty cycle, in order to prevent the pulmonarysystem from adapting to the therapy stimulation sequence and to maintaintherapy efficacy. In an example, the implantable system can beconfigured to provide a frequency hopping or varying frequencystimulation for anti-habituation.

In an example, the implantable system can activate, deactivate,increase, or decrease the blocking effect in response to one or morephysiological or other parameter. In certain examples, the blocking canbe increased or decreased in response to detected physical activity(e.g., physical activity sensed using a sensor, such as an accelerometercoupled to the implantable signal generator), the blocking can beactivated or deactivated in response to sensed physiological parameters(e.g., a bronchial diameter decrease sensed using a sensor, such as astrain gauge, an impedance sensor, or other electrical, mechanical, orother sensor, etc.).

In an example, the implantable system can modulate the therapy based ona circadian or other rhythm of the subject (e.g., sensed using a sleepsensor, time of day, clock, or other sensor), or the implantable systemcan modulate the therapy to provide for one or more periods of notherapy (e.g., user selected time periods), or by abstaining fromproviding therapy to one side of the bronchi while the other sidereceives therapy or vice versa, for example, to allow the autonomicsystem to provide general pulmonary maintenance, such as coughing, mucusclearance, mucus production, or other physiological response. Forexample, COPD subjects can be particularly susceptible during the earlymorning hours to exacerbation. As such, maximum therapy can be desirableduring this time period.

In other examples, the implantable system can be configured to delivertherapy during time periods of peak constriction or discomfort. Manysubjects have identifiable periods of maximum constriction ordiscomfort, such as in the morning following sleep, in the eveningbefore sleep, or during one or more other time periods. In an example,the implantable sensor can include a sleep sensor or posture sensorconfigured to detect and to inhibit therapy during sleep, or configuredto provide therapy following the detected cessation of sleep. In anexample, periods of maximum therapy or no therapy can be configuredusing population data, or can be configured using specific subject data.In an example, the implantable system can initially be configured usingpopulation or clinical data, and then can be adjusted according toindividual subject needs.

For example, if a specific subject commonly reports waking at or near aspecified time during sleep feeling short of breath or havingdiscomfort, the implantable system can be configured to provide therapyaround the reported time, relieving the discomfort of the subject.Further, therapy can automatically be provided following a detectedcessation of sleep. If the detected cessation is during a normal sleeptime of the subject, indicating that airway restriction or subjectdiscomfort caused the subject to wake, therapy can be provided.

In an example, the implantable system can be configured to cease therapyduring periods where therapy is not needed. In an example, the periodscan be identified using information from the subject, from a population,or the periods can be user-specified. For example, certain subjects feellittle to no constriction or discomfort during the afternoon. In thisexample, to conserve battery life, or to allow normal physiologicalresponse of the subject to resume, therapy can be prohibited during theidentified period.

In other examples, therapy can be switched off during periods ofexacerbation, such as COPD exacerbation. In an example, COPDexacerbation can include a worsening of COPD symptoms beyond normalday-to-day variation. In an example, exacerbation can be sensed usingone or more physiological parameters configured to monitor symptoms ofCOPD, such as breathlessness, cough, sputum or mucus production, color,or thickness, wheezing, thoracic pressure (e.g., chest tightness,pressure, or pain, etc.), or one or more other symptoms. In otherexamples, the implantable system can receive one or more otherindicators of exacerbation, such as hospitalization, or one or moreother user inputs indicating exacerbation.

In an example, therapy can be switched off during hospitalization, orduring one or more other physiological or time periods specified by aclinician. Hospitalization can be manually input, or automaticallydetermined using medical record data or one or more other source ofmedical information.

Cough

In an example, inhibiting nerve traffic to one or more lung, from one ormore lung, or both to and from one or more lung along one or more of thebronchi can block, inhibit, or reduce the urge of a subject to cough,for example, by reducing the ability of one or more of the bronchi tocontract, or by blocking afferent signals from receptors responsive togas, toxins, foreign matter, etc.

In an example, the implantable system can include one or more sensor(e.g., cough sensor) or input configured to receive an indication ofacute or chronic cough, such as a pressure sensor, a respiration sensor,a sound sensor, an activity sensor, an impedance sensor, a phrenic nerveinput, or other sensor configured to detect or receive an indication ofcough. In an example, the pressure sensor can be configured to detect achange in pressure in a body (e.g., airway, thorax, etc.) indicative ofa cough. In an example, the respiration sensor (e.g., tidal volumesensor, minute ventilation (MV) sensor, etc.) can be configured todetect a change in respiration indicative of a cough. In an example, thesound sensor (accelerometer, microphone, etc.) can be configured todetect a change in sound indicative of a cough. In an example, theactivity sensor (e.g., accelerometer, etc.) can be configured to detecta vibration, motion, or other activity of a subject indicative of acough. In an example, the impedance sensor can be configured to detectimpedance (e.g., a change in impedance) indicative of fluid (e.g.,mucus, etc.) buildup, accumulation, or a change in consistency of thelungs, bronchi, or airway indicative of a likely period of cough, ormucas buildup. In an example, one or more electrodes can be used tosense or detect phrenic nerve (or other nerve) activity indicative ofcough.

In an example, upon sensing or detecting acute or chronic cough, theimplantable system can be configured to inhibit nerve traffic along oneor more of the bronchi, blocking, inhibiting, or reducing the ability ofa subject to cough. In other examples, the implantable system can beconfigured to deliver therapy upon sensing or detecting a series ofcoughs, or coughing or a rate of coughing over a specified (e.g., userspecified) period of time (e.g., 1 minute, 5 minutes, etc,). In anexample, the inhibition can continue for a period of time (e.g., a timeperiod established by a clinician), after which, the therapy can cease,only to resume if the coughing continues or begins again followingtherapy.

In other examples, the implantable system can include one or moreuser-inputs configured to receive a user indication of cough, or auser-indicated cough event (e.g., a subject, clinician, or othercaregiver indication of cough, a subject-indicated, clinician-indicated,or other caregiver-indicated cough event, etc.). In an example, theimplantable system can be configured to receive input from an externaldevice configured to receive input from the user. In an example, theexternal device can include a subject control. As the subjectexperiences a cough or series of coughs, the subject can provide arequest, using the external device, to the implantable system to provideblocking therapy. In other examples, the external device can include amedical device programmer, or other clinician operated device. As thesubject is being treated for cough (e.g., chronic cough), the clinicianor other caregiver or user can provide a request to the implantablesystem, using the external device, to provide blocking therapy to treatthe coughing. Upon receiving the request or indication of cough, theimplantable system can deliver the blocking therapy, inhibiting nervetraffic both to and from the lungs, treating the cough.

In an example, after sensing or detecting cough, or upon receiving auser indication of cough, the blocking therapy can be delivered. In anexample, the blocking can be delivered for a period of time and thenstopped to ascertain whether the coughing or cough episode has ceased.In other examples, the blocking can be delivered until the sensing ordetecting an indication of cough has detected a cessation of cough, orthe blocking can be delivered until a user identified cessation of coughis received. If coughing continues, then the blocking signal can beresumed.

In other examples, the implantable system can be configured to allowcough (e.g., by stopping therapy), such as for mucus, sputum, or othermatter clearance during one or more therapy programs. Further, byblocking or inhibiting neural traffic on at least a portion of thebronchi, mucus production can be inhibited or reduced by blockingefferent signals configured to trigger mucus production.

Pulmonary Toilet

In an example, certain subjects (e.g., having chronic bronchitis, etc.)can benefit from productive cough, by allowing mucus or other foreignmatter to escape the lungs or bronchi. In an example, the mucus or otherforeign matter can be detected, such as by using a mucus or othersensor. In other examples, a user (e.g., a subject, a clinician, orother caregiver or user) can be configured to provide a normal or otherperiod of time where no therapy is to be delivered (e.g., no blockingsignal is to be provided to the subject), to allow for clearance ofmucus or other matter.

In an example, the time period can include a daily, hourly, or othernormal or other period configured to allow a time for normal pulmonarymaintenance, or to allow for the clearance of mucus or other matter inthe absence of, or in conjunction with, detected mucus or other foreignmatter buildup.

In an example, the time period can include a preset daily period (e.g.,15 minutes, 1 hour, etc.) occurring at a specific time of day (e.g., 8AM, 10 PM, etc.). In other examples, the time period can include aperiod of time after the subject has woken from sleep. In certainexamples, a sleep sensor, subject activity or posture sensor, or othersensor can be used to detect a sleep or awake state of the subject.

In other examples, the time period can include a more regular interval,such as “off” for 15 minutes and “on” for 45 minutes, “off” for 5minutes and “on” for 1 hour, etc.

Hyperinflation

In an example, the implantable system can be configured to detect andapply therapy during periods of hyperinflation. Hyperinflation occurs asinhalation increases faster than exhalation. In a healthy subject, asinhalation increases (e.g., during activity), exhalation increases toexpel the increased volume of air. However, if inhalation increases andexhalation does not increase, the subject's respiration baselineapproaches the maximum respiration capacity of the lungs, leaving thesubject short of breath and starved of oxygen. By dilating the bronchi,more air can be allowed to escape, increasing the ability of the subjectto exhale.

In an example, hyperinflation can be detected by a combination offactors, such as an increase in subject activity (e.g., indicative of anincreased respiratory need), an increase in breathing frequency, or adecrease in respiration volume. Once hyperinflation is detected, therapycan be provided or increased to increase the diameter of the bronchi,opening the airway.

Titrate Therapy with Drug Stimulation

In an example, the implantable system can be configured to provide theblocking signal in conjunction with drug stimulation. Many COPD subjectstake a drugs (e.g., spiriva, etc.) configured to prevent bronchospasm(narrowing of the airway), or to provide airway dilation. In an example,the implantable system can be configured to work with the drugstimulation to increase total efficacy of therapy.

For example, many subjects taking anticholinergic agents, such asspiriva, do so at set times (e.g., daily in the morning, etc.). Usingthe dosage and instructions for use, blocking therapy can be provided asthe effects of the anticholinergic begin to decrease, thereby extendingthe total effect of therapy.

In an example, if a subject receives a dose of an anticholinergic agentin the morning, the effect (e.g., measured forced expiratory volume(FEV)) increases initially, peaks, then gradually falls off. In anexample, as the effect of the drug begins to decline, blocking therapycan be provided to extend the total effect of therapy (e.g., byincreasing the total expiratory volume). In an example, once the subjectis determined to be asleep, or once the subject is instructed to receiveanother dose of the anticholinergic agent, blocking therapy can beceased.

Hyperplasia and Hypertrophy

Many COPD subjects have an enlarged, thick, or bulked bronchi reducingthe diameter of the airway due to hyperplasia (cell multiplication),hypertrophy (cell enlargement, muscle bulk), or both. In order toachieve maximum dilation of the bronchi, the muscles of the bronchi mustbe at rest, or debulked. In an example, providing a blocking signal andrelieving smooth muscle contraction can relax the muscles of thebronchi, over time, leading to a debulking of tissue or a loss of smoothmuscle tone.

In an example, a narrow bronchial passage can be detected using adetected pressure through the airway, using a detected volume of airthrough the airway, or using a relationship between both. In certainexamples, pressure can be detected in the bronchi. In other examples,other surrogates can be used, such as airway pressure in other parts ofthe respiratory system. In an example, an airway pressure or volume canbe detected using temperature sensors, detecting an air temperature dropalong a pathway.

In an example, once a narrow bronchial passage has been detected,therapy can be provided to relieve smooth muscle contraction. In certainexamples, the blocking therapy can be combined with one or more otherdebulking techniques, such as ablation, etc.

Pulse Generator

In an example, an implantable signal generator can be configured toreceive information from at least one sensor or other system componentand modulate the blocking signal using the received information. In anexample, the system component can include a component, such as aprocessor or other sensor or module, capable of generating an internallygenerated event, such as a clock or other marker or trigger. In otherexamples, the sensor can include one or more other physiologic or othersensors configured to sense physiologic or other information from thesubject.

Programmer

In an example, the system can include a clinician programmer configuredto be communicatively coupled (e.g., wirelessly coupled) to at least aportion of the implantable system, such as the implantable signalgenerator, etc. In an example, the clinician programmer can beconfigured to receive information from, or send information to, theimplantable signal generator. In other examples, the clinicianprogrammer can allow a clinician or other user to program or otherwisesend instructions to the implantable signal generator.

Subject Actuator

In an example, the system can include a subject programmer or subjectactuator configured to be communicatively coupled to at least a portionof the implantable system. In an example, the subject programmer canprovide for communication between the clinician programmer and theimplantable system, such as by acting as a repeater. The subjectprogrammer can be configured to communicate locally with the implantablesystem, and remotely with the clinician programmer.

In an example, the subject programmer can be configured to allow asubject to control, alter, or otherwise change at least one operatingcharacteristic of the implantable system. In an example, the subject canturn the implantable system on or off using the subject programmer orsubject actuator. In other examples, the subject programmer can beconfigured to communicate information to or from the subject to aclinician or the implantable system.

Battery

In other examples, the implantable system can include one or more otheraspects, such as a primary or secondary cell battery system havingvarious charging or re-charging capabilities. The battery system caninclude a primary cell, a secondary cell (e.g., rechargeable), or othertopology. The secondary cell topology can include or be coupled to acharging system, such as an inductively coupled, acoustically coupled,photonically coupled, or other coupled charging system.

Battery Charger

In an example, the system can include a battery charger. The batterycharger can include implantable components included in or coupled to theimplantable system, external components, or a combination of implantableand external components. In an example, the battery charger can beconfigured to wirelessly charge (e.g., inductively, etc.) theimplantable system. In an example, the implantable signal generator canbe implanted subcutaneously outside of the thorax, e.g., accessible formaintenance, battery charging or replacement, or for communicationoutside of the body.

Lead/Electrode

In an example, implantable system can include a multi-lead or multi-leadmulti-channel system. The multi-lead system can include one or moreleads, each having one or more electrodes. In certain examples, theleads or the electrodes can be electrically coupled, or can beelectrically independent from each other. In other examples, the leadsor electrodes can be electrically (e.g., directly, such as through alead) coupled to an implantable signal generator, or the leads orelectrodes can be wirelessly coupled to the implantable signalgenerator, such as by using one or more wireless transceivers orcommunication modules.

For example, a wireless lead can be implanted at the pulmonary nervesand communicate wirelessly with an implantable signal generator.Alternatively, a wireless lead could be placed endo-bronchially (withoutsurgery) and communicate with an implantable signal generator.

Telemetry

Further, the implantable system can include a telemetry system,configured to communicate between the implantable system and an externaldevice, such as unidirectionally or bidirectionally. The implantablesystem can be configured communicated wirelessly with the externaldevice, such as by inductive, RF, or other telemetry. The communicationcan be configured to transfer information between the implantable systemand the external device, such as one or more of programming information,physiological information, or other instructions or information.

Example Procedural Description and Steps

Intubate subject with a bifurcated endotracheal tube.

Position subject in lateral recumbent position with arm raised overhead, exposing both anterior and posterior chest walls on operativeside.

Ventilate subject on non-operative side only.

Make skin incisions and place ports using blunt dissection at desiredlocations on the anterior and posterior chest wall, typically from the4^(th) through 8^(th) rib interspaces.

Lung will collapse spontaneously once chest wall is violated and ET tubeis allowed to vent on operative side.

Insert thorascope and auxiliary tools through ports.

A combination of subject positioning (slightly rolled forward) andretraction may be used to cause the lung to roll anteriorly, exposingthe reflection of the parietal and visceral pleura.

Use careful blunt and sharp dissection to incise the reflection of thepleura at the bronchus.

Bluntly dissect connective tissue to isolate the bronchus at a distanceapproximately 1 to 4 cartilaginous “rings” from where the bronchusenters the lung parenchyma.

Care must be taken to avoid damage to the aorta or azygous vein(depending on side of surgery), pulmonary artery, and pulmonary vein.

Attach cuff electrode (with attached lead) to the dorsal aspect of thebronchus at a distance approximately 1 to 4 “rings” from the lungparenchyma.

Note: alternative electrode configurations may require differentattachment techniques. In the case of a loop electrode, blunt dissectionis carried out around the complete circumference of the bronchus. Asuture may be passes around the bronchus, which can then be used in turnto pull an electrode around the bronchus.

Loop the lead superiorly over the hilum of the lung, being careful notto kink, twist, or apply tension to the lead.

The lead may also be tunneled under the pleura for a distance along theinside of the chest wall.

At the desired location, typically on the anterior chest wall, the leadmay be tunneled between the ribs. On the exterior chest, the led may betunneled subcutaneously to a desired location for the signal generator,typically near the clavicle or on the abdominal wall.

Re-inflate the collapsed lung and reposition the subject to thecontralateral side.

Place the second electrode and lead analogously to the first.

Test each lead for appropriate and correct electrical contact andfunctioning.

Create a subcutaneous pocket for the signal generator at the desiredlocation.

Attach both leads and turn on the signal generator.

Insert bilateral chest tubes and close all incisions.

Chest tubes may be removed approximately 24 hours post operatively oncea chest X-ray confirms the absence of clinically significantpneumothorax and/or pleura effusion.

In an example, a subject can be intubated, such as by using a bifurcatedendotracheal tube or other appropriate medical instrument.

In an example, the subject can be positioned in a lateral recumbentposition with arm raised overhead, exposing both anterior and posteriorchest walls on operative side. In other examples, the subject can bepositioned in one or more other positions allowing access to the lungs.

In an example, the subject can be operated on a first side only, and canbe ventilated on the non-operative side. In an example, skin can be madeand ports can be placed using blunt dissection at one or more desiredlocations on the anterior or posterior chest wall. In an example, thedesired locations can be located between the 4th through 8th ribinterspaces.

Once the chest wall is violated, the lung can collapse, and theendotracheal tube can be used to provide ventilation on the operativeside. Once the lung is collapsed, medical instruments, such as athorascope or auxiliary tools, can be inserted through the ports.

In certain examples, a combination of subject positioning (slightlyrolled forward) and retraction can be used to cause the lung to rollanteriorly, exposing the reflection of the parietal and visceral pleura.

Once exposed, a careful blunt and sharp dissection can be used to incisethe reflection of the pleura at the bronchus. From there, connectivetissue can be bluntly dissected to isolate the bronchus, e.g., at adistance approximately 1 to 4 cartilaginous “rings” from where thebronchus enters the lung parenchyma. Care must be taken to avoid damageto the aorta or azygous vein (depending on side of surgery), pulmonaryartery, and pulmonary vein.

In an example, an electrode, such as a cuff electrode (with attachedlead) can be attached to the dorsal aspect of the bronchus at a distanceapproximately 1 to 4 “rings” from the lung parenchyma. In certainexamples, alternative electrode configurations can require differentattachment techniques. For example, in the case of a loop electrode,blunt dissection can be carried out around the complete circumference ofthe bronchus. A suture can be passed around the bronchus, which can thenbe used in turn to pull an electrode around the bronchus.

In an example, a lead coupled to the electrode can be looped superiorlyover the hilum of the lung, being careful not to kink, twist, or applytension to the lead.

In certain examples, the lead can also be tunneled under the pleura fora distance along the inside of the chest wall. At the desired location,typically on the anterior chest wall, the lead can be tunneled betweenthe ribs. On the exterior chest, the led may be tunneled subcutaneouslyto a desired location for the signal generator, typically near theclavicle or on the abdominal wall.

In an example, the collapsed lung can be re-inflated, and the subjectcan be repositioned to the contralateral side. Once re-positioned, thesubject can be operated on the second side, previously non-operativeside. Similar steps can be followed to place a second electrode on thesecond side analogously to the first electrode. Once implanted, eachlead for each electrode can be tested for appropriate and correctelectrical contact and functioning.

In an example, a subcutaneous pocket can be created for the signalgenerator at a desired location. Once the pocket is created, and thesignal generator is placed, both leads can be attached and the signalgenerator can be turned on.

In an example, bilateral chest tubes can be inserted and all incisionscan be closed. Following a recovery period, (e.g., 24 hours), andsuccessful testing to confirm the absence of clinically significantpneumothorax or pleura effusion (e.g., using a chest X-ray or othermethod), the chest tubes can be removed.

In other examples, one or more other methods can be used to implant thesignal generator and provide one or more electrodes coupled to orproximate one or more of the bronchi.

FIG. 1 illustrates generally an example of a system 100 including animplantable signal generator 101 and a processor 102 coupled to thesignal generator 101. In certain examples, the processor 102 can beincluded in, or can be separate from the implantable signal generator101. In an example, the processor 102 can include an external componentconfigured to be wirelessly coupled to the implantable signal generator101.

In an example, the implantable signal generator 101 can be configured togenerate a blocking signal to be delivered to at least a portion of abronchus of a subject. In an example, the blocking signal can beconfigured to inhibit efferent nerve traffic, afferent nerve traffic, orboth efferent and afferent nerve traffic between the central nervoussystem and at least a portion of the bronchus or a lung. In an example,the blocking signal can be configured to relieve bronchial smooth musclecontraction, and can inhibit cough, e.g., by blocking nerve signals toand from the respiratory anatomy.

In an example, the processor 102 can be configured to receiveinformation about an indication of cough. In certain examples, theinformation can include information from a user-identified indication ofcough, the information can include information from a sensor configuredto detect an indication of cough, or the information can includeinformation from both the user-identified indication and the sensor. Inan example, the processor 102 can be configured to control delivery ofthe blocking signal to the at least a portion of the bronchus, e.g., toinhibit cough.

FIG. 2 illustrates generally an example of a system 200 including animplantable signal generator 201 and a processor 202 coupled to thesignal generator 201. In certain examples, the system 200 can include atleast one of a cough sensor 203, a user-interface 204, or a mucus sensor205 coupled to the processor 202.

In an example, the cough sensor 203 can include one or more implantableor external sensors configured to detect an indication of cough. In anexample, the cough sensor 203 can be configured to detect a cough or anepisode of one or more coughs, and to provide information about thedetected cough or episode or one or more coughs to at least one of theprocessor 202 or the signal generator 201.

In an example, the user-interface 204 can include one or moreuser-inputs configured to receive information from a user (e.g., asubject, a clinician, a caregiver, or other user). In an example, theuser-interface 204 can be configured to receive information about anindication of cough from the user, and to provide information about theindication of cough to at least one of the processor 202 or the signalgenerator 201.

In an example, the user-interface 204 can include a subject-interface,configured to allow the subject to identify an undesired period ofcough, e.g., by pushing a button or providing one or more other inputs.In an example, information about the subject-identified undesired periodof cough can be provided to at least one of the processor 202 or thesignal generator 201.

In an example, the mucus sensor 205 can include one or more implantableor external sensors configured to detect mucus or other matter, or todetect a building or accumulation of mucus or other matter in the lungsor bronchi. In an example, the mucus sensor 205 can include an impedancesensor, or other sensor configured to detect the buildup or accumulationof mucus or fluid in the lungs or bronchi. In an example, the mucussensor 205 can be configured to provide information about the detectedmucus or other matter to at least one of the processor 202 or the signalgenerator 201.

FIG. 3 illustrates generally an example of a method 300 includingcontrolling delivery of a blocking signal to inhibit cough.

At 301, a blocking signal can be generated. In an example, the blockingsignal is generated using a signal generator, such as the implantablesignal generator 101.

At 302, information about an indication of cough is received, anddelivery of the blocking signal is controlled, using the receivedinformation, to inhibit cough.

FIG. 4 illustrates generally an example of a method 400 includingcontrolling delivery of a blocking signal to inhibit cough, or to allowmucus clearance.

At 401, a blocking signal is generated, for example, using a signalgenerator, such as the implantable signal generator 101.

At 402, information about an indication of cough is received. In anexample, the indication of cough can be received from at least one of acough sensor (e.g., the cough sensor 203 or other sensor configured todetect an indication of cough) or a user-interface (e.g., theuser-interface 204 or other user-input configured to receive auser-identified cough indication).

At 403, information about an indication of mucus building is received.In an example, the indication of mucus building can be received from amucus sensor, such as the mucus sensor 205 or other sensor configured todetect an indication of mucus or fluid accumulation in at least one of alung or bronchi.

At 404, delivery of the blocking signal can be controlled, usingreceived information, to inhibit cough or to allow mucus clearance. Inan example, the delivery of the blocking signal can be controlled usingthe received information about the indication of cough, about thereceived information about the indication of mucus buildup, or both. Inan example, the controlling the delivery of the blocking signal caninclude providing the blocking signal to at least a portion of thebronchi if an indication of cough is detected or received. In otherexamples, the controlling the delivery of the blocking signal caninclude not providing the blocking signal if an indication of mucusbuildup or other fluid or foreign matter is detected or received.

FIG. 5 illustrates generally an example of a method 500 includingdelivering a blocking signal.

At 501, information about an indication of cough is detected orreceived. In an example, the information can be detected or receivedusing at least one of a cough sensor (e.g., the cough sensor 203 orother sensor configured to detect an indication of cough) or auser-interface (e.g., the user-interface 204 or other user-inputconfigured to receive a user-identified indication of cough).

At 502, if an indication of cough is detected or received, then, at 503,information about an indication of mucus buildup is received. At 502, ifan indication of cough is not detected or received, then process flowreturns to 501.

At 504, if the information about the indication of mucus buildingindicates that mucus has not built up, then, at 505, a blocking signalis delivered configured to inhibit cough. In an example, a blockingsignal can be delivered to at least a portion of a bronchus using animplantable signal generator. In an example, the blocking signal can beconfigured to inhibit nerve traffic both to and from the lungs,relieving bronchial smooth muscle contraction and inhibiting cough. Inother examples, the blocking signal can be configured to inhibit mucusproduction.

At 504, if the information about the indication of mucus buildingindicates that mucus has built up, then process flow returns to 503. Inan example, once the mucus buildup is cleared, e.g., by cough, then theblocking signal can be delivered to inhibit cough. In certain examples,the blocking signal can be ceased for a specified time to allow formucus clearance, or the blocking signal can be ceased until anindication of mucus or fluid clearance is received using the mucussensor.

In certain examples, if cough continues, but mucus is not cleared,information can be provided to a user, a clinician, or other caregiver,such as using an alarm or other notification. In other examples, otherinformation, such as the information about the indication of cough ormucus buildup, can be provided.

FIGS. 6A and 6B illustrate generally structures in a thorax duringaccess, including an incised pleura at a parietal-visceral reflection.FIG. 6A illustrates a left mediastinum exposure, including a leftinferior pulmonary vein 603, a left main bronchus 604, a left pulmonaryartery 605, a left posterior pulmonary plexus 606, and a deflated leftlung 607. FIG. 6B illustrates a right mediastinum exposure, including aright main bronchus 608, an azygous vein 609, a right posteriorpulmonary plexus 610, and a right lung 611.

In these examples, a first instrument 601, such as a fiberscope, athoracoscope, or other instrument, can enter the thorax, such as intothe sixth rib interspace, and a second tool 602, such as a dissectiontool or other instrument, can enter the thorax, such as into the fourthrib interspace. In other examples, at least one of the first or secondinstruments 601, 602, can access the thorax at one or more otherlocations.

Generally, working between the spine and its associated vascularstructure and the deflated lung, an incision in the pleura can be madeat the reflection of the parietal pleura and the visceral pleuraallowing access to the dorsal aspect of the main bronchi. In the exampleof FIG. 6A, a descending aorta is close to the spinal column and is leftundisturbed. In the example of FIG. 6B, the azygous vein 609 is close tothe spinal column and is left undisturbed. In an example, once thedorsal aspect of the main bronchi has been accessed, an electrode (e.g.,a cuff electrode, patch electrode, etc.) can be affixed to the dorsalaspect of the main bronchi near where the bronchi enter the lungparenchyma.

FIGS. 7-10 illustrate generally examples of various signal generatorimplant sites, lead paths, electrode sites, and electrodeconfigurations.

FIG. 7 illustrates generally an example of a system 700 including animplantable signal generator 701, a lead 702 coupled to the implantablesignal generator 701, and an electrode 703 coupled to the lead 702. Inthis example, the electrode can be affixed to or otherwise associatedwith the dorsal aspect of the main bronchi. The lead can be attached tothe electrode and can exit the thoracic cavity between the ribs. Whileother exit locations can be used, it can be convenient to use theexisting access port. Once the lead exits the thoracic cavity, it can betunneled subcutantiously to a convenient location for placing theimplantable signal generator.

In the example of FIG. 7, the implantable signal generator is located ina low lumbar, pararenal location. In other examples, the implantablesignal generator can be located in other locations in the body, such asin the thorax, or other subcutaneous locations. In other examples, thesignal generator can be located outside of the body, with the leadexiting to connect externally.

FIG. 8 illustrates generally an example of a system 800 including animplantable signal generator 801, a lead 802 coupled to the implantablesignal generator 801, and first and second cuff electrodes 803, 804coupled to the left and right bronchi.

FIG. 9 illustrates generally an example of a system 900 including firstand second partial cuff electrodes 901, 902 coupled to the left andright bronchi.

FIG. 10 illustrates generally an example of a system 1000 includingfirst and second patch electrodes 1001, 1002 coupled to the left andright bronchi.

FIGS. 11A-11C illustrate generally example electrode configurations in,on, or surrounding at least a portion of a bronchus. FIG. 11Aillustrates an example patch electrode configuration coupled to or nearat least a portion of a dorsal side of a bronchus. FIG. 11B illustratesgenerally an example partial cuff electrode configuration coupled to ornear the dorsal side of a bronchus. FIG. 11C illustrates generally anexample full cuff electrode configuration coupled to, surrounding, ornear at least a portion of a dorsal and ventral side of the bronchus. Inother examples, other electrode configurations can be used. In anexample, these, or other electrodes or electrode configurations, can beconfigured to be placed on the posterior (e.g., membranous aspect) ofthe bronchi.

FIGS. 12A-12D illustrate generally an endo-bronchial electrodeconfiguration and approach. FIG. 12A illustrates generally a dorsal viewof a left lung 1200, a right lung 1201, a bronchi 1202, and pulmonaryparasympathetic nerves 1203, 1204.

FIG. 12B illustrates generally an example of a wireless electrode 1206and an antenna 1207 located in a trachea 1208 proximate pulmonaryparasympathetic nerves 1205. In other examples, one or more wireless orother electrodes can be placed in the trachea 1208 or other locationproximate the pulmonary parasympathetic sympathetic nerves 1205, or oneor more other nerves.

FIG. 12C illustrates generally an example of a silastic patch 1209, oneor more electrodes 1212 (e.g., plunge or other electrodes), an embeddedantenna 1210, and a control circuit 1211. In an example, the one or moreelectrodes 1212 can be sized or spaced be close to one or more dorsalpulmonary nerves, such as pulmonary parasympathetic nerves 1205.

FIG. 12D illustrates generally an example of an implantable nervestimulation pulse generator 1213 coupled (e.g., using one or more leads)to subcutaneously transmitting antennas 1214, 1215 on either side of asternum 1216. In an example, the nerve stimulation pulse generator 1213can be configured to deliver energy to one or more endo-bronchialelectrode. In other examples, the endo-bronchial electrodes, such as theone or more electrodes 1212 can be configured to communicate with thenerve stimulation pulse generator 1213, or other implantable pulsegenerator, using the subcutaneously transmitting antennas 1214, 1215, orone or more other communication or telemetry devices.

FIG. 13 illustrates generally a relationship between a bony structureand lungs, and an example of accessing the root of the main bronchiusing two ports.

In an example, one or more ports can be placed between the ribs at anylocation between the shoulder blade and the spinal column, and from thesecond rib down to the tenth rib (typically at the fourth through eighthrib interspaces). In other examples, access can be gained lateral to theshoulder blade and along the anterior (i.e., ventral) aspect of thethorax.

In this example, a right lung 1301 is shown to be deflated and fallinglateral and anterior within the thoracic cavity. In an example, thefirst port can be located approximately at the fourth rib interspace andthe second port can be located approximately at the sixth ribinterspace. Various instruments, such as a fiberscope 1302, a dissectiontool 1303, etc., can be inserted through the first or the second port.

OTHER EXAMPLES

In an example, a system can include an implantable signal generatorconfigured to generate a blocking signal to be delivered to at least aportion of a bronchus of a subject. In an example, the blocking signalcan be configured to inhibit nerve traffic both to and from a lung ofthe subject, to relieve bronchial smooth muscle contraction, and toinhibit cough and mucus production.

In certain examples, the system can include a mucus sensor, configuredto detect an indication of mucus buildup in at least a portion of thebronchus. Further, the system can include a processor, communicativelycoupled to the implantable signal generator and the mucus sensor, theprocessor configured to control delivery of the blocking signal, and tostop delivery of the blocking signal, using the indication of mucusbuildup, to allow mucus clearance.

In this example, the blocking signal can be provided for sustainedperiods of time, or according to one or more therapy algorithms (e.g.,having a duty cycle, a scheduled “on” and “off” time, etc.). If theindication of mucus buildup is received, the therapy algorithm can beinterrupted to provide for a period of no blocking signal, configured toallow cough and clear built up mucus.

Further, in certain examples, the blocking signal can be provided toinhibit mucus production.

Some Notes

The above detailed description includes references to the accompanyingdrawings, which form a part of the detailed description. The drawingsshow, by way of illustration, specific embodiments in which theinvention can be practiced. These embodiments are also referred toherein as “examples.” All publications, patents, and patent documentsreferred to in this document are incorporated by reference herein intheir entirety, as though individually incorporated by reference. In theevent of inconsistent usages between this document and those documentsso incorporated by reference, the usage in the incorporated reference(s)should be considered supplementary to that of this document; forirreconcilable inconsistencies, the usage in this document controls.

In this document, the terms “a” or “an” are used, as is common in patentdocuments, to include one or more than one, independent of any otherinstances or usages of “at least one” or “one or more.” In thisdocument, the term “or” is used to refer to a nonexclusive or, such that“A or B” includes “A but not B,” “B but not A,” and “A and B,” unlessotherwise indicated. In the appended claims, the terms “including” and“in which” are used as the plain-English equivalents of the respectiveterms “comprising” and “wherein.” Also, in the following claims, theterms “including” and “comprising” are open-ended, that is, a system,device, article, or process that includes elements in addition to thoselisted after such a term in a claim are still deemed to fall within thescope of that claim. Moreover, in the following claims, the terms“first,” “second,” and “third,” etc. are used merely as labels, and arenot intended to impose numerical requirements on their objects.

Method examples described herein can be computer-implemented at least inpart. Some examples can include a computer-readable medium ormachine-readable medium encoded with instructions operable to configurean electronic device to perform methods as described in the aboveexamples. An implementation of such methods can include code, such asmicrocode, assembly language code, a higher-level language code, or thelike. Such code can include computer readable instructions forperforming various methods. The code may form portions of computerprogram products. Further, the code may be tangibly stored on one ormore volatile or non-volatile computer-readable media during executionor at other times. These computer-readable media may include, but arenot limited to, hard disks, removable magnetic disks, removable opticaldisks (e.g., compact disks and digital video disks), magnetic cassettes,memory cards or sticks, random access memories (RAM's), read onlymemories (ROM's), and the like. Further, in certain examples, aprocessor configured to perform a function or operation can include oneor more processors, each configured to perform at least a portion of thefunction or operation.

The above description is intended to be illustrative, and notrestrictive. For example, the above-described examples (or one or moreaspects thereof) may be used in combination with each other. Otherembodiments can be used, such as by one of ordinary skill in the artupon reviewing the above description. The Abstract is provided to complywith 37 C.F.R. § 1.72(b), to allow the reader to quickly ascertain thenature of the technical disclosure. It is submitted with theunderstanding that it will not be used to interpret or limit the scopeor meaning of the claims. Also, in the above Detailed Description,various features may be grouped together to streamline the disclosure.This should not be interpreted as intending that an unclaimed disclosedfeature is essential to any claim. Rather, inventive subject matter maylie in less than all features of a particular disclosed embodiment.Thus, the following claims are hereby incorporated into the DetailedDescription, with each claim standing on its own as a separateembodiment. The scope of the invention should be determined withreference to the appended claims, along with the full scope ofequivalents to which such claims are entitled.

What is claimed is:
 1. A method of treating a subject for inflammation,hypertrophy, or constriction of smooth muscles lining the bronchi of anairway of the subject, or excessive mucus production of the subject, themethod comprising: positioning an electrode proximate to tissuepositioned along a bronchus or trachea of the subject, the electrodebeing operatively coupled to a signal generator; and delivering energyfrom the signal generator via the electrode to the tissue to block,inhibit, or reduce the ability of the subject to produce mucus.
 2. Themethod of claim 1, the method further comprising: detecting mucus orother matter in the lungs or bronchi, a building or accumulation ofmucus or other matter in the lungs or bronchi, or combinations thereofusing one or more sensors.
 3. The method of claim 2, wherein the one ormore sensors are mucus sensors.
 4. The method of claim 3, wherein theone or more mucus sensors comprises an impedance sensor.
 5. The methodof claim 1, wherein positioning the electrode proximate to tissuepositioned along a bronchus or trachea of the subject comprisesimplanting the electrode proximate nerve tissue located along the airwayin the subject.
 6. The method of claim 1, the method further comprising:implanting the signal generator in the subject, wherein the signalgenerator is configured to generate a cough production inhibitingblocking signal to be delivered to at least a portion of nerve tissuepositioned along the bronchus or trachea of the subject, wherein thecough production inhibiting blocking signal is configured to inhibit atleast one of nerve traffic to or from a lung of the subject to relievebronchial smooth muscle contraction and to inhibit cough.
 7. The methodof claim 1, the method further comprising: implanting the signalgenerator in the subject, wherein the signal generator configured togenerate a cough stimulating signal to be delivered to at least aportion of nerve tissue positioned along the bronchus or trachea of thesubject, wherein the cough stimulating signal is configured to stimulateat least one of nerve traffic to or from a lung of the subject totrigger bronchial smooth muscle contraction and to stimulate cough. 8.The method of claim 1, wherein positioning the electrode proximate totissue positioned along a bronchus or trachea of the subject comprisesplacing the electrode in or around the bronchus.
 9. The method of claim1, wherein delivering energy comprises delivering a sufficient amount ofenergy to the tissue to cause cessation of mucus production, and whereinthe method further comprises stopping energy delivery to the tissuebased on detection of the cessation of mucus production.
 10. The methodof claim 1, wherein delivering energy comprises delivering a sufficientamount of energy to the tissue to cause stimulation of cough, andwherein the method further comprises stopping energy delivery to thetissue based on detection of mucus clearance.
 11. The method of claim 1,wherein generator is configured to generate a blocking signal to bedelivered to the at least one electrode to cause the at least oneelectrode to deliver the energy to the tissue, wherein the blockingsignal is configured to inhibit nerve traffic to a lung of the subject.12. The method of claim 1, wherein delivering energy to the tissue isbased on a circadian rhythm of the subject.
 13. The method of claim 12,wherein the circadian rhythm of the subject is measured using a sleepsensor, time of day, clock, or combinations thereof.
 14. The method ofclaim 1, wherein delivering energy provides energy to one side of thebronchi while the other side receives no energy.
 15. The method of claim1, wherein delivering energy blocks or inhibits neural traffic on atleast a portion of the bronchi to inhibit or reduce mucus production byblocking efferent signals configured to trigger mucus production.
 16. Amethod for inhibiting or reducing mucus production by a subject, themethod comprising: delivering energy via at least one electrode operablycoupled to a generator to tissue on at least a portion of the bronchi ofthe subject to inhibit or reduce mucus production.
 17. The system ofclaim 16, wherein mucus production is reduced or inhibited by blockingefferent signals configured to trigger mucus production.